PROTEIN HORMONES AND THE EUCARYOTIC GENOME: A GENERAL THEORY OF HORMONE ACTION I. D. RAACKE* Hormones have been studied extensively and intensively for roughly a century now, and there is a correspondingly large accumulation of observations made by many people in a succession of ever more sophisticated disciplines, starting with clinical medicine and progressing through gross anatomy, histology, physiology, biochemistry, and pure organic chemistry. Though this work has culminated in the knowledge of the exact chemical structure of most classical hormones, including protein hormones (see [I]), as well as in their chemical syntheses, it is curious that a large part of present work on hormones is again at the cellular and physiological level, although the techniques are more sophisticated. This seeming retrogression indicates that something along the journey has been missed or that a dead end necessitates a "second look" or the exploration of new approaches. The fact is that the chemical structures of the hormones have not yielded the expected clues as to their mode of action, just as the masses of data on their observed physiological and biochemical effects have brought us no answer to the fundamental question ofwhat a hormone is. In most cases we have much information about what a hormone does, or, more accurately, what it appears to do, but in not a single case do we know exactly how it exerts its primary action (although we might be getting there, as I will discuss below). Therefore, the classical definition of hormone given by Starling in 1905 [2], as substances, "chemical messengers," that are made in one tissue (ductless glands) and carried through the blood to stimulate another, though meaningless in any fundamental way, is still as good as any other. Ofcourse, Starling's definition reflects the medical origins of endocrinology, for it neglects creatures like plants (for reviews ofvarious aspects of plant growth substances see, for example, [3; 4; 5, pp. 191, 196, 207, 216, 223, 228]), or even unicellular fungi [6, 7] that have neither blood nor ductless glands, but which nevertheless possess substances generally recognized as hormones. One might, therefore, mod- *Department of Biology, Boston University, Boston, Massachusetts 02215. Perspectives in Biology and Medicine ¦ Autumn 1977 139 ernize Starling's definition and say simply that hormones are substances produced by one kind of cell and exert their action on another type. To use "cell" instead of "gland" not only removes phylogenetic restrictions, but is also in keeping with the fact that glands are cytologically heterogeneous and that the hormone is produced by one particular type of cell within the glandular tissue. Furthermore, by not requiring that the hormone enter the bloodstream, but simply the interstitial cell fluid, one would remove the restriction implicit in Starling's definition that a hormone act at a point more or less distant from its point of origin. Since hormones, then, could even act as signals between adjacent cells, this would allow one to place a number of substances, now somewhat in limbo, under the hormone umbrella, most particularly the brain peptides known as "hormone releasing substances" (R.F.)—as, for example, corticotropic-releasing factor, CRF or cortioliberin, according to the latest nomenclature [8] (for reviews see [9-11])—and the grammatically cumbersome "hormone release inhibiting factors" (RFI)—as, for example , somatotropin (GH) release-inhibiting factor or somatostatin ([12], also [10, H])—as well as the whole class of recently emerging "growth substances" or "mitogens" [13-18]. Still, this does not change the definition in any profound way and does little more than increase the range of substances to which the label "hormone" can be applied. Nevertheless, Starling's definition was, and in a more limited way continues to be, useful, for it implied a dual strategy: to understand the underlying chemical mechanism, or the chemical "message" carried by hormones, and to correlate these with the observed gross physiological effects. This, in essence, was the goal of each succeeding generation of endocrinologists, bringing to bear the ever more sophisticated techniques of a variety of disciplines on the problem. There was, thus, a sustained effort over the years to improve on Starling's definition. There was also a strong pervasive feeling in the field, especially among workers on...

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ISSN

1529-8795

Print ISSN

0031-5982

Pages

pp. 139-157

Launched on MUSE

2015-01-07

Open Access

No

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